Azacitidine Injection

Azacitidine Injection is used for: Myelodysplastic Syndromes, Juvenile Myelomonocytic Leukemia

Myelodysplastic Syndromes Indicated for myelodysplastic syndromes in patients with the following French-American-British (FAB) subtypes: Refractory anemia (RA) or RA with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), chronic myelomonocytic leukemia (CMMoL) Each cycle is 4 weeks 75 mg/m2 IV or SC daily for 7 days; repeat cycle every 4 weeks May be increased to 100 mg/m2 if no benefit is observed after 2 treatment cycles and if no toxicity other than nausea and vomiting Treat for a minimum of 4-6 cycles Continue treatment as long as the patient continues to benefit

Juvenile Myelomonocytic Leukemia Indicated for juvenile myelomonocytic leukemia (JMML) in children aged >1 month >1 month to <1 year OR weighs <10 kg: 2.5 mg/kg IV once daily for 7 days in a 28-day cycle >1 year AND weighs >10 kg: 75 mg/m2 IV once daily for 7 days in a 28-day cycle Treat for at least 3 cycles; not to exceed 6 cycles May delay dose up to 14 days for nonhematologic toxicities May continue treatment for up to 6 cycles if the patient continues to benefit

Renal impairment Mild-severe (CrCl 15-89 mL/min): No dosage adjustment necessary Monitor patients with severe renal impairment (CrCl 15-29 mL/min) more frequently and modify dosage for adverse reactions

IV Preparation Reconstitute each vial with 10 mL sterile water for injection Vigorously shake or roll vial until all solids are dissolved; resulting concentration is 10 mg/mL; solution should appear clear Visually inspect parenteral drug product for particulate matter and discoloration before administration, whenever solution and container permit Adults: Withdraw required amount and inject into a 50 -100 mL infusion bag of either 0.9% NaCl or Lactated Ringer Pediatric patients: Withdraw required amount of drug solution and inject into an infusion bag (volume up to 100 mL) of either 0.9% NaCl or Lactated Ringer to achieve a final concentration of 0.9-4 mg/mL IV Administration IV administration only when reconstituted with 10 mL of sterile water Administer total dose over a period of 10 - 40 min; complete administration within 1 hr of reconstitution SC Preparation Reconstitute with 4 mL room temperature sterile water for injection for immediate use and refrigerated sterile water (2-8C, 36-46F) for delayed use; inject diluent slowly into vial Vigorously shake or roll the vial until a uniform suspension is achieved; suspension will be cloudy; resulting concentration is 25 mg/mL Do not filter suspension after reconstitution; filtering could remove the active substance For doses requiring >1 vial, divide dose equally between the syringes (eg, dose 150 mg = 6 mL, 2 syringes with 3 mL in each syringe) and inject into 2 separate sites Due to retention in vial and needle, it may not be feasible to withdraw all of the suspension from vial SC Administration SC administration only when reconstituted with 4 mL of sterile water Resuspend the contents of syringe to provide a homogeneous suspension immediately before administration To resuspend, vigorously roll syringe between the palms until a uniform, cloudy suspension is achieved Rotate sites for each injection (thigh, abdomen, or upper arm) Administer new injections at least 1 inch from an old site and never into areas where the site is tender, bruised, red, or hard

Advanced malignant hepatic tumors Hypersensitivity to azacitidine or mannitol

Risks of Substitution with Other Azacitidine Products: Do not substitute Azacitidine IV for oral azacitidine. Anemia, Neutropenia and Thrombocytopenia. Hepatotoxicity: Patients with severe preexisting hepatic impairment are at higher risk for toxicity. Renal Toxicity: Monitor patients with renal impairment for toxicity since azacitidine and its metabolites are primarily excreted by the kidneys. Tumor Lysis Syndrome: Azacitidine may cause fatal or serious tumor lysis syndrome, including in patients with MDS. Assess baseline risk and monitor and treat as appropriate. Embryo-Fetal Toxicity: Azacitidine can cause fetal harm. Advise female patients and male patients with female partners of the reproductive potential of the potential risk to a fetus and to use effective contraception. Monitoring Parameters Monitor liver function tests, serum creatinine, and serum bicarbonate before initiation of treatment and before each treatment cycle. Monitor all patients for hematologic response and for renal toxicity; delay or reduce the dosage as appropriate Monitor full blood count before initiation of treatment, before each treatment cycle, and as clinically indicated. Monitor for bleeding.

Pregnancy Based on its mechanism of actions and animal studies, fetal harm may occur when administered to pregnant females No data available on use in pregnant females to evaluate for drug-associated risks Verify pregnancy status of females of reproductive potential before initiating treatment Animal data Teratogenic and caused embryofetal lethality in animals at doses less than the recommended human dose of azacitidine Advise pregnant females of the potential risk to fetus Contraception IV or SC Use effective contraception during treatment and for 6 months after last dose Advise males with female partners of reproductive potential to use effective contraception during treatment with this medication and for 3 months after last dose Lactation There is no information regarding presence of azacitidine in human milk, effects of therapy on breastfed infant, or effects of therapy on milk production IV or SC: Because many drugs are excreted in human milk and because of potential for tumorigenicity shown for azacitidine in animal studies and potential for serious adverse reactions in nursing infants, advise patients not to breastfeed during treatment and for 1 week after the last dose

Side effects of Azacitidine IV : >10% (SC or IV) All grades Nausea (48-71%) Anemia (51-70%) Thrombocytopenia (66-70%) Neutropenia (32-66%) Constipation (34-50%) Vomiting (27-54%) Pyrexia (30-52%) Leukopenia (18-48%) Injection site erythema (35-43%) Diarrhea (36%) Ecchymosis (31%) Dyspnea (29%) Injection site reaction (14-29%) Petechiae (24%) Fatigue (24%) Injection site pain (23%) Arthralgia (22%) Headache (22%) Anorexia (21%) Dizziness (19%) Injection site pain (5-19%) Erythema (17%) Febrile neutropenia (14-16%) Chest pain (16%) Myalgia (16%) Nasopharyngitis (15%) Rash (14%) Injection site bruising (5-14%) Abdominal pain (13%) Upper respiratory tract infection (13%) Anxiety (13%) Abdominal tenderness (12%) Malaise (11%) Pneumonia (11%) Insomnia (11%) Grade 3-4 Anemia (44%) Thrombocytopenia (34%) Neutropenia (28%) Pyrexia (18%) Fatigue (12%) Nausea (12%) 1-10% (SC or IV) All grades Gingival bleeding (10%) Hematoma (6-9%) Hypertension (9%) Lethargy (8%) Stomatitis (8%) Injection site pruritus (7%) Hypotension (7%) Anemia aggravated (6%) Loose stools (6%) Urticaria (6%) Postprocedural hemorrhage (6%) Dyspepsia (6%) Injection site rash (6%) Injection site swelling (5%) Injection site pigmentation changes (5%) Injection site induration (6%) Skin nodule (5%) Injection site granuloma (5%) Chest wall pain (5%) Dry skin (5%) Mouth hemorrhage (5%) <5% Blood and lymphatic system disorders: Agranulocytosis, bone marrow failure, pancytopenia splenomegaly Cardiac disorders: Atrial fibrillation, cardiac failure, cardiac failure congestive, cardiorespiratory arrest, congestive cardiomyopathy Eye disorders: Eye hemorrhage Gastrointestinal disorders: Diverticulitis, gastrointestinal hemorrhage, melena, perirectal abscess General disorders and administration site conditions: Catheter site hemorrhage, general physical health deterioration, systemic inflammatory response syndrome Hepatobiliary disorders: cholecystitis. Immune system disorders: anaphylactic shock, hypersensitivity Infections and infestations: Abscess limb, bacterial infection, cellulitis, blastomycosis, injection site infection, Klebsiella sepsis, neutropenic sepsis, pharyngitis streptococcal, pneumonia Klebsiella, sepsis, septic shock, Staphylococcal bacteremia, Staphylococcal infection, toxoplasmosis Metabolism and nutrition disorders: Dehydration Musculoskeletal and connective tissue disorders: Bone pain aggravated, muscle weakness, neck pain Neoplasms benign, malignant and unspecified: Leukemia cutis Nervous system disorders: Cerebral hemorrhage, convulsions, intracranial hemorrhage Renal and urinary disorders: Loin pain, renal failure Respiratory, thoracic and mediastinal disorders: Hemoptysis, lung infiltration, pneumonitis, respiratory distress Skin and subcutaneous tissue disorders: Pyoderma gangrenosum, rash pruritic, skin induration. Surgical and medical procedures: cholecystectomy Vascular disorders: Orthostatic hypotension Grade 3-4 Febrile neutropenia (10%) Constipation (8%) Abdominal pain (7%) Vomiting (7%) Dyspnea (5%) Hypertension (4%) Petechiae (4%) Upper respiratory tract infection (4%) Erythema (3%) Pharyngolaryngeal pain (3%) Insomnia (3%) Hypokalemia (3%) Urinary tract infection (3%) Leukopenia (2%) Dyspepsia (2%) Hematuria (2%) Pruritus (2%) Lethargy (2%) Rash (1%) Dyspnea exertional (1%) Rash (1%) Anxiety (1%) Rhinitis (1%)

Pyrimidine analog of cytidine that inhibits DNA/RNA methyltransferases Azacitidine is incorporated into RNA and DNA following cellular uptake and enzymatic biotransformation to nucleotide triphosphates Hypomethylation of DNA and direct cytotoxic effect on abnormal hematopoietic cells in bone marrow

Azacitidine 100mg/ml Injection manufactured by ZAS Corporation. Its generic name is Azacitidine IV. Azacitidine is availble in Bangladesh. Farmaco BD drug index information on Azacitidine Injection is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.